Production of optically pure materials is increasingly important in the chemical industry, particularly in the production of agricultural and pharmaceutical chemicals. In particular, in many of these chemicals, one optically active isomer provides the desired biological or pharmaceutical activity, while other optical isomers are either inactive or produce an adverse or unwanted biological or chemical effect. In the manufacture of these chemicals, there is a need to isolate one specific isomer as an end product.
Heretofore, two methods have been employed to achieve isomer isolation. One method comprises a stereospecific synthesis where one optically active isomer is made to the exclusion of the others, and the other comprises an optical separation where the various isomers are concurrently made and then physically separated from one another using separation columns. In the case of stereospecific synthesis, in-situ measurement of the optically active constituent provides a technique for monitoring the progress of the reaction. On the other hand, for separation methods, in-situ measurement of optical activity of the effluent from the separation column provides a technique for determining when the appropriate optically active isomer is eluting.
Once the optically pure material is manufactured, it typically is blended at some point in time with other materials, which may or may not be optically active, to provide a desired formulation for end use. In the blending operation, the measurement of optical activity of the blend provides a technique for determining when the specified formulation is obtained.
Manual and automatic polarimeters are available for measuring the concentration of optically active constituents in a fluid medium, for example, as detectors in the liquid chromatographic separation of stereoisomers. These polarimeters operate by illuminating one surface of a liquid containing the steroisomers with polarized light and detecting with a polarized analyzer the emerging light from the opposite surface. In these polarimeters, the polarization axis of the incident light is fixed and known while the polarization axis of the analyzer is variable and also known. Measurement of the optical activity of the liquid requires that a static or dynamic liquid sample be placed into the polarimeter between a polarized light source and the polarized analyzer. The axially spaced light source and analyzer provide a single light path of appropriate length through the liquid sample. The necessity of placing the liquid sample between the light source and the analyzer has limited the application of these polarimeters in the in-situ analysis of optically active constituents in chemical manufacturing and formulation processes.